The aims of this project are to investigate the natural history of bladder cancer in mice and man using cell and molecular biological approaches. The central approach to this work is the use of gene transfer techniques to study the effects of known transforming genes in different bladder epithelial cell lines, both mouse and human, and to look for alternative routes of transformation in bladder cancer. The aims of the proposal are: 1. To identify alternative routes of transformation in bladder cancer using NIH/3T3 cells with in vivo selection and by developing new recipients for DNA transfection. 2. To study the expression of characterized transforming genes in different epithelial cell types to establish the effects of the differentiation and growth characteristics of these cells in vitro and in vivo. 3. To examine the timing and expression of ras gene products in bladder carcinogenesis and to study the mode of action of different transforming genes and define cellular targets involved in epithelial transformation.